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1.
Medicine (Baltimore) ; 99(44): e22847, 2020 Oct 30.
Article in English | MEDLINE | ID: covidwho-20238619

ABSTRACT

Numerous cases of pneumonia from a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China during December 2019.We determined the correlations of patient parameters with disease severity in patients with COVID-19.A total of 132 patients from Wuhan Fourth Hospital who had COVID-19 from February 1 to February 29 in 2020 were retrospectively analyzed.Ninety patients had mild disease, 32 had severe disease, and 10 had critical disease. The severe/critical group was older (P < .05), had a higher proportion of males (P < .05), and had a greater mortality rate (0% vs 61.9%, P < .05). The main symptoms were fever (n = 112, 84.8%) and cough (n = 96, 72.7%). Patients were treated with antiviral agents (n = 94, 71.2%), antibiotics (n = 92, 69.7%), glucocorticoids (n = 46, 34.8%), intravenous immunoglobulin (n = 38, 27.3%), and/or traditional Chinese medicine (n = 40, 30.3%). Patients in the severe/critical group received mechanical ventilation (n = 22, 16.7%) or high-flow nasal can-nula oxygen therapy (n = 6, 4.5%). Chest computed tomography (CT) indicated bilateral pneumonia in all patients. Relative to the mild group, the severe/critical group had higher levels of leukocytes, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, B-type natriuretic peptide (BNP), liver enzymes, and myocardial enzymes (P < .05), and decreased levels of lymphocytes and blood oxygen partial pressure (P < .05).The main clinical symptoms of patients from Wuhan who had COVID-19 were fever and cough. Patients with severe/critical disease were more likely to be male and elderly. Disease severity correlated with increased leukocytes, CRP, PCT, BNP, D-dimer, liver enzymes, and myocardial enzymes, and with decreased lymphocytes and blood oxygen partial pressure.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Retrospective Studies , SARS-CoV-2
2.
Int J Mol Sci ; 24(11)2023 Jun 05.
Article in English | MEDLINE | ID: covidwho-20244913

ABSTRACT

We previously identified a lipopeptide, EK1C4, by linking cholesterol to EK1, a pan-CoV fusion inhibitory peptide via a polyethylene glycol (PEG) linker, which showed potent pan-CoV fusion inhibitory activity. However, PEG can elicit antibodies to PEG in vivo, which will attenuate its antiviral activity. Therefore, we designed and synthesized a dePEGylated lipopeptide, EKL1C, by replacing the PEG linker in EK1C4 with a short peptide. Similar to EK1C4, EKL1C displayed potent inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses. In this study, we found that EKL1C also exhibited broad-spectrum fusion inhibitory activity against human immunodeficiency virus type 1 (HIV-1) infection by interacting with the N-terminal heptad repeat 1 (HR1) of viral gp41 to block six-helix bundle (6-HB) formation. These results suggest that HR1 is a common target for the development of broad-spectrum viral fusion inhibitors and EKL1C has potential clinical application as a candidate therapeutic or preventive agent against infection by coronavirus, HIV-1, and possibly other class I enveloped viruses.


Subject(s)
COVID-19 , HIV Fusion Inhibitors , HIV Infections , HIV-1 , Humans , Lipopeptides/pharmacology , SARS-CoV-2 , Anti-Retroviral Agents , HIV Envelope Protein gp41 , HIV Fusion Inhibitors/pharmacology
3.
Virus Res ; 329: 199103, 2023 05.
Article in English | MEDLINE | ID: covidwho-2288833

ABSTRACT

A variety of swine enteric coronaviruses (SECoVs) have emerged and are prevalent in pig populations, including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome (SADS)-CoV, a newly identified bat-origin CoV with zoonotic potential. Unfortunately, available traditional, inactivated and attenuated SECoV vaccines are of limited efficacy against the variants currently circulating in most pig populations. In this study, we evaluated the role of host factor heat shock protein 90 (Hsp90) as an antiviral target against SECoVs, exemplified by SADS-CoV. Pharmacological inhibition of Hsp90 diminished SADS-CoV replication significantly in porcine and human cell lines, and also decreased replication of SADS-CoV in a porcine intestinal enteroid model. Further mechanistic experiments revealed that both porcine and human isoforms of Hsp90 interact with the SADS-CoV nucleocapsid (N) protein, and inhibition of Hsp90 resulted in autophagic degradation of N protein. Moreover, we linked Hsp90 to virus-induced cellular pyroptosis, as SADS-CoV was found to trigger caspase-1/gasdermin-d-mediated pyroptotic cell death, which was mitigated by inhibition of Hsp90. Finally, we demonstrated that Hsp90 also associated with N proteins and was involved in propagation of PEDV, PDCoV and TGEV. This study thus extends our understanding of immune responses to SADS-CoV infection and offers a new potential therapeutic option against four SECoVs.


Subject(s)
Alphacoronavirus , Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Transmissible gastroenteritis virus , Animals , Humans , Alphacoronavirus/genetics , Antiviral Agents/pharmacology , Heat-Shock Proteins , Swine , HSP90 Heat-Shock Proteins/metabolism
4.
J Biol Chem ; 299(5): 104668, 2023 05.
Article in English | MEDLINE | ID: covidwho-2288832

ABSTRACT

Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90ß on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b were found to be novel clients of Hsp90ß in particular. Pharmacological inhibition of Hsp90 with 17-DMAG results in N protein proteasome-dependent degradation. Hsp90 depletion-induced N protein degradation is independent of CHIP, a ubiquitin E3 ligase previously identified for Hsp90 client proteins, but alleviated by FBXO10, an E3 ligase identified by subsequent siRNA screening. We also provide evidence that Hsp90 depletion may suppress SARS-CoV-2 assembly partially through induced M or N degradation. Additionally, we found that GSDMD-mediated pyroptotic cell death triggered by SARS-CoV-2 was mitigated by inhibition of Hsp90. These findings collectively highlight a beneficial role for targeting of Hsp90 during SARS-CoV-2 infection, directly inhibiting virion production and reducing inflammatory injury by preventing the pyroptosis that contributes to severe SARS-CoV-2 disease.


Subject(s)
COVID-19 , HSP90 Heat-Shock Proteins , Pyroptosis , SARS-CoV-2 , Virion , Humans , COVID-19/pathology , COVID-19/physiopathology , COVID-19/virology , HSP90 Heat-Shock Proteins/metabolism , SARS-CoV-2/chemistry , SARS-CoV-2/growth & development , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Ubiquitin-Protein Ligases/metabolism , Virion/chemistry , Virion/growth & development , Virion/metabolism , Viral Proteins/metabolism
5.
Int J Rheum Dis ; 26(4): 759-763, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2286142

ABSTRACT

BACKGROUND: Clinically amyopathic dermatomyositis (CADM) is characterized by typical skin lesions with no (amyopathic) or subclinical (hypomyopathic) evidence of muscle involvement. Patients with CADM may also develop rapidly progressive interstitial lung disease (ILD), and have a poor prognosis. However, the diagnosis of rapidly progressive ILD faces a challenge during the severe acute respiratory syndrome coronavirus 2 pandemic. Severe acute respiratory syndrome and ground-glass attenuation on a chest computed tomography scan are the presenting features in both conditions. CASE PRESENTATION: A 45-year-old woman with amyopathic dermatomyositis had acute onset of fever and dyspnea in February 2020. She had abnormal lung findings on CT scan. Polymerase chain reaction testing for SARS-CoV-2 was not available at that time. Chest CT revealed non-specific manifestations that could be either the signs of ILD or SARS-CoV-2 infection. Antiviral therapy was initiated with oseltamivir. Three days later, she had erythema on face, palm, and back. The ratio of lactate dehydrogenase (LDH) isoenzyme 3 to total LDH was elevated. The ratio of LDH isoenzyme 1 to total LDH was declined. Therefore, she was transferred to the rheumatology ward for further treatment. However, she died from respiratory failure 2 weeks later. CONCLUSIONS: We speculate that the altered LDH isoenzyme pattern may be an early biomarker for co-occurrence of CADM and ILD.


Subject(s)
COVID-19 , Dermatomyositis , Lung Diseases, Interstitial , Female , Humans , Middle Aged , Dermatomyositis/complications , Dermatomyositis/diagnosis , Dermatomyositis/drug therapy , COVID-19/complications , Pandemics , Isoenzymes/therapeutic use , SARS-CoV-2 , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Autoantibodies
6.
Exp Ther Med ; 25(5): 200, 2023 May.
Article in English | MEDLINE | ID: covidwho-2269813

ABSTRACT

The serology test of SARS-CoV-2 is one of the critical assays to make a diagnosis of SARS-CoV-2 infection. The gold immunochromatography assay (GICA) is a common measure to test SARS-CoV-2 specific IgG and IgM. The sensitivity and specificity of the assay are ~>80%. It has been reported that the result of GICA could be compromised in various situations, such as auto-immune diseases, Kawasaki disease, pregnancy or other conditions. However, following the European Hematology Association's consensus statement on the management of Waldenström's Macroglobulinemia (WM) patients, serological tests for SARS-CoV-2 specific IgM should not be affected by the total IgM or paraprotein levels. The present study reports a patient with duplicate positive serology tests of SARS-CoV-2 which is hypothesized to be due to monoclonal IgM caused by WM.

7.
Virol Sin ; 2022 Sep 24.
Article in English | MEDLINE | ID: covidwho-2258965

ABSTRACT

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally, from B.1.17 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) to B.1.1.529 (Omicron). The emerging or re-emerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics, pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 â€‹cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 â€‹cells. We utilized both animal models of human ACE2 (hACE2) transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.

8.
Front Psychol ; 13: 1047680, 2022.
Article in English | MEDLINE | ID: covidwho-2163111

ABSTRACT

The COVID-19 pandemic led higher education institutions to transition to online learning. The present study was designed to investigate students' self-regulated learning strategies on academic performance in online learning. We analyzed the differences in college students' self-regulated learning (SRL) strategies according to their grade point average (GPA). The study included 1,163 students at a distance education university in China. Two online questionnaires were used to determine online SRL strategies. GPA scores were obtained from the university exam database to determine academic performance. The analysis showed that there are great differences between different self-regulated strategies and between different students when accepting the online learning. The analysis also showed that self-evaluation, metacognitive self-regulation, and effort regulation were positive predictors of academic progress, besides, self-evaluation and effort regulation had mutual influence effect on the improvement of GPA in online learning. These data will help teachers, education policymakers, and education administrators adopt and implement online learning services to improve students' academic performance.

9.
Zool Res ; 43(6): 1041-1062, 2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2111387

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques ( Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multi-organ dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019 (COVID-19). Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway, which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy (an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection, which may facilitate the development of therapeutic interventions for COVID-19.


Subject(s)
COVID-19 , Animals , COVID-19/genetics , COVID-19/veterinary , Macaca mulatta , SARS-CoV-2 , Transcriptome , Viral Load/veterinary
10.
EBioMedicine ; 85: 104297, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2117785

ABSTRACT

BACKGROUND: Increasing severe morbidity and mortality by simultaneous or sequential infections with SARS-CoV-2 and influenza A viruses (IAV), especially in the elderly and obese patients, highlight the urgency of developing a combination vaccine against COVID-19 and influenza. METHODS: Self-assembling SARS-CoV-2 RBD-trimer and Influenza H1N1 HA1-trimer antigens were constructed, upon the stable fusion core in post-fusion conformation. Immunogenicity of SARS-CoV-2 RBD-trimer vaccine and H1N1 HA1-trimer antigens candidates were evaluated in mice. Protection efficacy of a combination vaccine candidate against SARS-CoV-2 and IAV challenge was identified using the K18-hACE2 mouse model. FINDINGS: Both the resultant RBD-trimer for SARS-CoV-2 and HA1-trimer for H1N1 influenza fully exposed receptor-binding motifs (RBM) or receptor-binding site (RBS). Two-dose RBD-trimer induced significantly higher binding and neutralizing antibody titers, and also a strong Th1/Th2 balanced cellular immune response in mice. Similarly, the HA1-trimer vaccine was confirmed to exhibit potent immunogenicity in mice. A combination vaccine candidate, composed of RBD-trimer and HA1-trimer, afforded high protection efficacy in mouse models against stringent lethal SARS-CoV-2 and homogenous H1N1 influenza co-infection, characterized by 100% survival rate. INTERPRETATION: Our results represent a proof of concept for a combined vaccine candidate based on trimerized receptor binding domain against co-epidemics of COVID-19 and influenza. FUNDING: This project was funded by the Strategic Priority Research Program of CAS (XDB29040201), the National Natural Science Foundation of China (81830050, 81901680, and 32070569) and China Postdoctoral Science Foundation (2021M703450).


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Mice , Humans , Animals , SARS-CoV-2 , COVID-19 Vaccines , COVID-19/prevention & control , Antibodies, Neutralizing , Antibodies, Viral , Vaccines, Combined
11.
Antiviral Res ; 208: 105450, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2085916

ABSTRACT

FB2001 is a drug candidate that targets the main protease of SARS-CoV-2 via covalently binding to cysteine 145. In this study, we evaluated the inhibitory activities of FB2001 against several SARS-CoV-2 variants in vitro and in vivo (in mice), and we also evaluated the histopathological analysis and immunostaining of FB2001 on lung and brain which have been rarely reported. The results showed that FB2001 exhibited potent antiviral efficacy against several current SARS-CoV-2 variants in Vero E6 cells, namely, B.1.1.7 (Alpha): EC50 = 0.39 ± 0.01 µM, EC90 = 0.75 ± 0.01 µM; B.1.351 (Beta): EC50 = 0.28 ± 0.11 µM, EC90 = 0.57 ± 0.21 µM; B.1.617.2 (Delta): EC50 = 0.27 ± 0.05 µM, EC90 = 0.81 ± 0.20 µM; B.1.1.529 (Omicron): EC50 = 0.26 ± 0.06 µM and EC50 = 0.042 ± 0.007 µM (in the presence of a P-glycoprotein inhibitor). FB2001 remained potent against SARS-CoV-2 replication in the presence of high concentrations of human serum, which indicating that human serum had no significant effect on the in vitro inhibitory activity. Additionally, this inhibitor exhibited an additive effect against SARS-CoV-2 when combined with Remdesivir. Furthermore, FB2001 significantly reduced the SARS-CoV-2 copy numbers and titers in the lungs and brains in vivo, and alleviated the pathological symptoms. In addition, FB2001 could alleviated local bleeding, erythrocyte overflow, edema, and inflammatory cell infiltration in brain tissue, and inhibitors reducing viral titers and improving inflammation in the brain have been rarely reported. A physiologically based pharmacokinetic model was established and verified to predict the FB2001 concentration in human lungs. When FB2001 was administered at 200 mg twice a day for 5 days, the observed Ctrough ss in plasma and predicted Ctrough ss of lung total concentration were 0.163 and 2.5 µg/mL, which were approximately 9 and 132-fold higher than the EC50 of 0.019 µg/mL (0.042 µM) against Omicron variant. Taken together, our study suggests that FB2001 is a promising therapeutic agent in COVID-19 treatment and can be combined with remdesivir to achieve improved clinical outcomes. Owing to its good safety and tolerability in healthy human (NCT05197179 and NCT04766931), FB2001 has been approved for Phase II/III clinical trial (NCT05445934).


Subject(s)
COVID-19 Drug Treatment , Coronavirus Infections , Pneumonia, Viral , Animals , Humans , Mice , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pandemics , Pneumonia, Viral/drug therapy , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , SARS-CoV-2 , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic
14.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1989752

ABSTRACT

COVID-19, caused by SARS-CoV-2, has resulted in hundreds of millions of infections and millions of deaths worldwide. Preliminary results exhibited excellent efficacy of SARS-CoV-2 vaccine in preventing hospitalization and severe disease. However, data on inactivated vaccine-induced immune responses of naturally infected patients are limited. Here, we characterized SARS-CoV-2 RBD-specific IgG (anti-S-RBD IgG) and neutralizing antibodies (NAbs) against SARS-CoV-2 wild type and variants of concerns (VOCs), as well as RBD-specific IgG-secreting B cells and antigen-specific T cells respectively in 51 SARS-CoV-2 recovered subjects and 63 healthy individuals. In SARS-CoV-2 recovered patients, a single dose vaccine is sufficient to reactivate robust anti-S-RBD IgG and NAbs. The neutralizing capacity against VOCs increased significantly post-vaccination no matter healthy individuals or SARS-CoV-2 recovered patients. In addition, RBD-specific IgG-secreting B cells in SARS-CoV-2 recovered patients were significantly higher than that in healthy vaccine recipients. After the vaccine booster, the frequencies of specific IFN-γ+ CD4+ T cell, IL-2+ CD4+ T cell, and TNF-α+ CD4+ T cell responses were significantly increased in SARS-CoV-2 recovered patients. Our data highlighted the safety and utility of SARS-CoV-2 inactivated vaccine and demonstrated that robust humoral and cellular immune response can be reactivated by one-dose inactivated vaccine in SARS-CoV-2 recovered patients.

15.
Front Immunol ; 13: 925922, 2022.
Article in English | MEDLINE | ID: covidwho-1933699

ABSTRACT

Although feline coronavirus (FCoV) infection is extremely common in cats, there are currently few effective treatments. A peptide derived from the heptad repeat 2 (HR2) domain of the coronavirus (CoV) spike protein has shown effective for inhibition of various human and animal CoVs in vitro, but further use of FCoV-HR2 in vivo has been limited by lack of practical delivery vectors and small animal infection model. To overcome these technical challenges, we first constructed a recombinant Bacillus subtilis (rBSCotB-HR2P) expressing spore coat protein B (CotB) fused to an HR2-derived peptide (HR2P) from a serotype II feline enteric CoV (FECV). Immunogenic capacity was evaluated in mice after intragastric or intranasal administration, showing that recombinant spores could trigger strong specific cellular and humoral immune responses. Furthermore, we developed a novel mouse model for FECV infection by transduction with its primary receptor (feline aminopeptidase N) using an E1/E3-deleted adenovirus type 5 vector. This model can be used to study the antiviral immune response and evaluate vaccines or drugs, and is an applicable choice to replace cats for the study of FECV. Oral administration of rBSCotB-HR2P in this mouse model effectively protected against FECV challenge and significantly reduced pathology in the digestive tract. Owing to its safety, low cost, and probiotic features, rBSCotB-HR2P is a promising oral vaccine candidate for use against FECV/FCoV infection in cats.


Subject(s)
Coronavirus Infections , Coronavirus, Feline , Animals , Bacillus subtilis/genetics , CD13 Antigens/metabolism , Cats , Coronavirus, Feline/genetics , Coronavirus, Feline/metabolism , Disease Models, Animal , Humans , Immunity , Mice , Peptides/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Spores, Bacterial/genetics
16.
Innovation in aging ; 5(Suppl 1):805-805, 2021.
Article in English | EuropePMC | ID: covidwho-1781922

ABSTRACT

Introduction: Growing research supports the use of older volunteers to provide respite and community-based assistance to persons with ADRD and their caregivers. This study explores the impact of COVID-19 on a face-to-face, peer-led psychoeducational intervention for African American ADRD family caregivers, the Senior Companion Program Plus (SCP-Plus), and its subsequent need to ‘pivot’ during the pandemic. Method: The SCP-Plus was a randomized control trial across three states that assessed program impact on ADRD family caregiver stress/burden, coping, and social support. In spring 2020, the SCP-Plus intervention was halted because of the potential risk to participants due to COVID-19 (n = 20 enrolled dyads). In an effort to maintain rapport and trust, critical to retention in research studies, team members began weekly (March-April) and then bi-weekly calls (May-December) for the purpose of providing a social check-in and to provide updates on the status of the intervention. Results: A total of 396 calls lasting approximately 10 minutes each were completed. Participants shared concerns around safety, access to food/supplies/masks/testing, feelings of stress and loss, concern for others, and the importance of technology as a means of social connection. Although the intervention aspect of the SCP-Plus ultimately ended due to COVID-19, information gleaned from these check-ins were used to pivot the study. The study moved forward by using a descriptive phenomenological approach to capture dyads’ lived experiences during COVID-19. Discussion: Overall, purposeful participant engagement through weekly/bi-weekly phone calls suggests that this is a promising strategy for participant retention as well as for pivoting research.

17.
Blood Sci ; 2(3): 76-78, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1784407

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the third zoonotic coronavirus to have an outbreak in the first two decades of the 21st century. Human-to-human transmission of this virus has threatened thousands of lives around the world. SARS-CoV-2 shares 79% and 50% sequence homology with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Like SARS-CoV and MERS-CoV infection, evidence has shown that SARS-CoV-2 infection also causes acute tissue damage due to a pathological immune response, particularly in severe cases. T cells play an important role in virus clearance and prevention, and in this paper, we summarize dynamic changes in the T cell count, subsets, phenotype, and function in Coronavirus Disease 2019 (COVID-19) patients based on current clinical reports. This review may help to better understand the pathological immune response of T cells and facilitate making better therapeutic strategies for patients with SARS-CoV-2 infection.

18.
Int J Environ Res Public Health ; 19(8)2022 04 11.
Article in English | MEDLINE | ID: covidwho-1785690

ABSTRACT

INTRODUCTION: To help older adults cope with loneliness during COVID-19, a weekly, telephone-based intergenerational program called "Big and Mini" was created in April 2020 to link young and older adults together. As part of an evaluation of Big and Mini, a survey with both close and open-ended questions was sent to participants. METHODS: A total of 63 Bigs and 53 Minis completed the survey. Their stress compared to before COVID-19, loneliness, life satisfaction, intergenerational closeness, and satisfaction with the program were measured for participants. Descriptive, bivariate correlation and conventional content analyses were conducted. RESULTS: On average, Bigs and Minis had participated in the program for 3.73 and 3.49 months, respectively. Approximately half of the Bigs (47.6%) and Minis (52.8%) felt the same stress level compared to before COVID-19. A few participants felt "less stressed" compared to before COVID -9 (14.3 and 7.5%, respectively, for Bigs and Minis). All participants reported medium levels of loneliness, high levels of satisfaction with life, satisfaction with the program, and intergenerational closeness. Content analysis suggested that the reasons to join or expectations of the program were friendship, mutually beneficial intergenerational connections, and coping with loneliness. CONCLUSIONS: The Big and Mini program offers a promising approach with mutual benefits for participants. Strategies to improve the program and implications for intergenerational programs are presented.


Subject(s)
COVID-19 , Adaptation, Psychological , Aged , COVID-19/epidemiology , Humans , Loneliness , Personal Satisfaction , Surveys and Questionnaires
19.
Viruses ; 14(3)2022 03 13.
Article in English | MEDLINE | ID: covidwho-1742726

ABSTRACT

The prolonged duration of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has resulted in the continuous emergence of variants of concern (VOC, e.g., Omicron) and variants of interest (VOI, e.g., Lambda). These variants have challenged the protective efficacy of current COVID-19 vaccines, thus calling for the development of novel therapeutics against SARS-CoV-2 and its VOCs. Here, we constructed a novel fusion inhibitor-based recombinant protein, denoted as 5-Helix, consisting of three heptad repeat 1 (HR1) and two heptad repeat 2 (HR2) fragments. The 5-Helix interacted with the HR2 domain of the viral S2 subunit, the most conserved region in spike (S) protein, to block homologous six-helix bundle (6-HB) formation between viral HR1 and HR2 domains and, hence, viral S-mediated cell-cell fusion. The 5-Helix potently inhibited infection by pseudotyped SARS-CoV-2 and its VOCs, including Delta and Omicron variants. The 5-Helix also inhibited infection by authentic SARS-CoV-2 wild-type (nCoV-SH01) strain and its Delta variant. Collectively, our findings suggest that 5-Helix can be further developed as either a therapeutic or prophylactic to treat and prevent infection by SARS-CoV-2 and its variants.


Subject(s)
COVID-19 , Viral Envelope Proteins , COVID-19 Vaccines , Humans , Membrane Glycoproteins/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/metabolism
20.
Medicine (Baltimore) ; 101(9): e28976, 2022 Mar 04.
Article in English | MEDLINE | ID: covidwho-1730760

ABSTRACT

ABSTRACT: The Corona Virus Disease 2019 (COVID-19) pandemic has huge impacts on the world, including human health and economic decline. The COVID-19 has severe infectivity, especially the elderly with chronic diseases will cause various complications after infection and accelerate the disease process. In addition, COVID-19 will also affect their mental health. Therefore, the mental health of elderly patients with chronic diseases cannot be ignored. The aim of this study was to investigate the well-being level of elderly people with chronic disease during COVID-19 postpandemic period in Beijing and analysis related influencing factors, so as to provide a basis for improving the well-being level of elderly chronic patients during the postpandemic period.Elderly patients with chronic diseases who met the inclusion criteria in 5 different administrative regions in Beijing were selected to carry out a questionnaire survey. The contents of the questionnaire included general data, the Memorial University of Newfoundland Happiness scale and the awareness situation of the COVID-19 pandemic. A total of 500 questionnaires were distributed by WeChat and 486 valid questionnaires were collected. The t test and one-way analysis of variance were used to compare Memorial University of Newfoundland Happiness scores between 2 or more groups, multiple linear regression analysis was used to conduct multiple factor analysis to explore the related factors about well-being level of elderly chronic patients.A total of 109 cases (22.43%) were evaluated high well-being level, 319 cases (65.64%) were evaluated moderate well-being level and 58 cases (11.93%) were evaluated low well-being according to the Memorial University of Newfoundland Happiness (MUNSH) scores rating. The multiple linear regression indicated that the education level, number of chronic diseases, medical expenses, frequency of children's visits, taking care of grandchildren or not, and group activity frequency significantly affected the well-being of patients with chronic diseases during COVID-19 postpandemic period in Beijing (P < .05).Most elderly patients with chronic diseases had moderate or above sense of well-being during postpandemic period, but we should still pay attention to the mental health of those elderly chronic patients with low education level, much comorbidity, more medical expenses, less visits by children, not take care of grandchildren and never participate in group activities.


Subject(s)
COVID-19/epidemiology , Chronic Disease/epidemiology , Aged , Aged, 80 and over , Child , China/epidemiology , Health Status , Humans , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
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